Precise correlation between MRI and histopathology - Exploring treatment margins for MRI-guided localized breast cancer therapy

Department of Radiology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, The Netherlands.
Radiotherapy and Oncology (Impact Factor: 4.36). 11/2010; 97(2):225-32. DOI: 10.1016/j.radonc.2010.07.025
Source: PubMed


Magnetic resonance imaging (MRI) is more often considered to guide, evaluate or select patients for partial breast irradiation (PBI) or minimally invasive therapy. Safe treatment margins around the MRI-visible lesion (MRI-GTV) are needed to account for surrounding subclinical occult disease.
To precisely compare MRI findings with histopathology, and to obtain detailed knowledge about type, rate, quantity and distance of occult disease around the MRI-GTV.
Patients undergoing MRI and breast-conserving therapy were prospectively included. The wide local excision specimens were subjected to detailed microscopic examination. The size of the invasive (index) tumor was compared with the MRI-GTV. The gross tumor volume (GTV) was defined as the pre-treatment visible lesion. Subclinical tumor foci were reconstructed at various distances to the MRI-GTV.
Sixty-two patients (64 breasts) were included. The mean size difference between MRI-GTV and the index tumor was 1.3mm. Subclinical disease occurred in 52% and 25% of the specimens at distances ≥10mm and ≥20mm, respectively, from the MRI-GTV.
For MRI-guided minimally invasive therapy, typical treatment margins of 10mm around the MRI-GTV may include occult disease in 52% of patients. When surgery achieves a 10mm tumor-free margin around the MRI-GTV, radiotherapy to the tumor bed may require clinical target volume margins >10mm in up to one-fourth of the patients.

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    • "We used the pathology data from the MARGINS (Multi-modality Analysis and Radiological Guidance IN breast-conServing therapy ) study to model the MSD quantity and spread distribution in the breasts of patients with early breast cancer eligible for breast conserving therapy [11]. More than 1800 microscopic slides of invasive breast cancers in 60 patients (48 patients with age > 50 and 12 with age 6 50) were examined by two experienced breast cancer pathologists [12] [13]. MSD was observed on the microscopic slides. "
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    ABSTRACT: Age is an important prognostic marker of patient outcome after breast conserving therapy; however, it is not clear how age affects the outcome. This study aimed to explore the relationship between age with the cell quantity and the radiosensitivity of microscopic disease (MSD) in relation to treatment outcome. We employed a treatment simulation framework which contains mathematic models for describing the load and spread of MSD based on a retrospective cohort of breast pathology specimens, a surgery simulation model for estimating the remaining MSD quantity and a tumor control probability model for predicting the risk of local recurrence following radiotherapy. The average MSD cell quantities around the primary tumor in younger (age⩽50years) and older patients were estimated at 1.9∗10(8)cells and 8.4∗10(7)cells, respectively (P<0.01). Following surgical simulation, these numbers decreased to 2.0∗10(7)cells and 1.3∗10(7)cells (P<0.01). Younger patients had smaller average surgical resection volume (118.9cm(3)) than older patients (162.9cm(3), P<0.01) but larger estimated radiosensitivity of MSD cells (0.111Gy(-1) versus 0.071Gy(-1), P<0.01). The higher local recurrence rate in younger patients could be explained by larger clonogenic microscopic disease cell quantity, even though the microscopic disease cells were found to be more radiosensitive. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Radiotherapy and Oncology 01/2015; 114(3). DOI:10.1016/j.radonc.2015.01.010 · 4.36 Impact Factor
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    • "This enables differentiation between the tumor and benign lesions like post-biopsy hematomas or cysts. Furthermore, MRI has a high sensitivity for detection of invasive breast cancer and a good correlation with histopathology findings [24,25]. However, standard diagnostic MRI is performed in prone position, while patients in most departments are irradiated in supine position. "
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    ABSTRACT: Accurate tumor bed delineation after breast-conserving surgery is important. However, consistency among observers on standard postoperative radiotherapy planning CT is low and volumes can be large due to seroma formation. A preoperative delineation of the tumor might be more consistent. Therefore, the purpose of this study was to determine the consistency of preoperative target volume delineation on CT and MRI for breast-conserving radiotherapy. Tumors were delineated on preoperative contrast-enhanced (CE) CT and newly developed 3D CE-MR images, by four breast radiation oncologists. Clinical target volumes (CTVs) were created by addition of a 1.5 cm margin around the tumor, excluding skin and chest wall. Consistency in target volume delineation was expressed by the interobserver variability. Therefore, the conformity index (CI), centre of mass distance (dCOM) and volumes were calculated. Tumor characteristics on CT and MRI were scored by an experienced breast radiologist. Preoperative tumor delineation resulted in a high interobserver agreement with a high median CI for the CTV, for both CT (0.80) and MRI (0.84). The tumor was missed on CT in 2/14 patients (14%). Leaving these 2 patients out of the analysis, CI was higher on MRI compared to CT for the GTV (p < 0.001) while not for the CTV (CT (0.82) versus MRI (0.84), p = 0.123). The dCOM did not differ between CT and MRI. The median CTV was 48 cm3 (range 28-137 cm3) on CT and 59 cm3 (range 30-153 cm3) on MRI (p < 0.001). Tumor shapes and margins were rated as more irregular and spiculated on CE-MRI. This study showed that preoperative target volume delineation resulted in small target volumes with a high consistency among observers. MRI appeared to be necessary for tumor detection and the visualization of irregularities and spiculations. Regarding the tumor delineation itself, no clinically relevant differences in interobserver variability were observed. These results will be used to study the potential for future MRI-guided and neoadjuvant radiotherapy.Trial registration: International Clinical Trials Registry Platform NTR3198.
    Radiation Oncology 02/2014; 9(1):63. DOI:10.1186/1748-717X-9-63 · 2.55 Impact Factor
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    • "However, these strategies do not necessarily address the accuracy in tumor bed definition. While some studies have correlated pathology to multimodal imaging [63] [64] [65] and others have addressed inter-/intra-fractional TBV variations [23,66–68], these studies mostly focus on tumor bed margins required for EB APBI and have been conducted with small patient series. We see a need for a systemic, multidisciplinary investigation involving radiology, surgery, pathology, radiation oncology, and medical physics. "
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    ABSTRACT: In recent years, accelerated partial breast irradiation (APBI) has been considered an alternative to whole breast irradiation for patients undergoing breast-conserving therapy. APBI delivers higher doses of radiation in fewer fractions to the post-lumpectomy tumor bed with a 1-2cm margin, targeting the area at the highest risk of local recurrence while sparing normal breast tissue. However, there are inherent challenges in defining accurate target volumes for APBI. Studies have shown that significant interobserver variation exists among radiation oncologists defining the lumpectomy cavity, which raises the question of how to improve the accuracy and consistency in the delineation of tumor bed volumes. The combination of standardized guidelines and surgical clips significantly improves an observer's ability in delineation, and it is the standard in multiple ongoing external-beam APBI trials. However, questions about the accuracy of the clips to mark the lumpectomy cavity remain, as clips only define a few points at the margin of the cavity. This paper reviews the techniques that have been developed so far to improve target delineation in APBI delivered by conformal external beam radiation therapy, including the use of standardized guidelines, surgical clips or fiducial markers, pre-operative computed tomography imaging, and additional imaging modalities, including magnetic resonance imaging, ultrasound imaging, and positron emission tomography/computed tomography. Alternatives to post-operative APBI, future directions, and clinical recommendations were also discussed.
    Radiotherapy and Oncology 06/2013; 108(2). DOI:10.1016/j.radonc.2013.05.028 · 4.36 Impact Factor
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